Magnetic Resonance Investigation of Hemoglobin from Sickle Deteriorated Erythrocytes

  • Henry M. Zeidan
Part of the Biodeterioration Research book series (BIOR, volume 3)

Abstract

Sickle hemoglobin under physiological conditions and concentrations aggregates upon de oxygenation to form a viscous gel composed of long fibers consisting of filaments of stacked rings, of which several detailed structures have been proposed (Finch et al., 1973). The important change in sickle hemoglobin is substitution of a non-polar hydrophobic residue (valine) for a polar residue (glutamic acid). This suggests that hydrophobic interactions are important in stabilizing HbS aggregation (Votano et al., 1977). A variety of small molecules containing hydrophobic moieties have been shown to inhibit the aggregation or gelation of deoxygenated HbS (Novak et al. 1978, 1979). These agents include aryalalkanes (Ross and Subramanian, 1977), the aromatic amino acids (Noguchi and Schechter, 1977, 1978), aliphatic alchols, amides and ureas (Poillon, 1980), a variety of oligopeptides (Kubota and Yang, 1977; Votano et al., 1977; Gorecki et al., 1980), and a variety of phenyl derivatives (Gorecki et al., 1980; Poillon, 1982). The inhibitory effects of these agents are believed to be due to a competitive interference mechanism in which the inhibitor binds to the HbS molecule at one of the important contact sites, and blocks other HbS molecules from binding at that site (Abraham et al., 1975; Behe and Englander, 1979).

Keywords

Electron Paramagnetic Resonance Spin Label Aromatic Moiety Magnetic Resonance Investigation Nitroxide Spin Label 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Abraham, E.C., Walker, D., Gravely, M. and Huisman, T.H. (1975). Minor hemoglobins in sickle cell anemia, B-thalaj-ssemi and related conditions. A study of red cell fractions isolated by density gradient centrifugation. Biochem. Med., 13, 56–77.CrossRefGoogle Scholar
  2. Baldwin, J.M. (1980). The structure of human carboxy hemoglobin at 2.7A° resolution, J. Mol. Biol., 136:103–128.CrossRefGoogle Scholar
  3. Behe, M.J. and Englander, S.W. (1979). Quantitative assessment of the non covalent inhibition of sickle hemoglobin gelation by phenyl derivatives and other known agents. Biochem., 18, 4196–4201.CrossRefGoogle Scholar
  4. Benesch, R.E., Benesch, R., and Yung, S. (1973). Equations for the spectrophotometric analysis of hemoglobin mixtures. Anal. Biochem., 55, 245–248.CrossRefGoogle Scholar
  5. Bertini, I. and Luchino, C. (1986). Unpaired electron-nuclear coupling detected by NMR: Nuclear relaxation NMR of paramagnetic molecules in biological systems, pp. 49–79, The Benjamin/Cummings Publishing Company, Inc., CA.Google Scholar
  6. Bolton, P.H., Mirau, P.A., Shater, R.H. and James, T.L. (1981). Interaction of anti-malarial of drug feuroquine with DNA, transfer RNA and poly A: 19-F-NMR chemical shift and relaxation, optical absorption and fluorescence studies. Biopolymers, 20, 435–449.CrossRefGoogle Scholar
  7. Chien, J.C. (1979). Electron paramagnetic resonance crystallography of spin-labeled hemoglobin protein fine structures. J. Mol. Bio., 133, 385–395.CrossRefGoogle Scholar
  8. DeVanx, P., Davonust, J.P. and Rousselet, A. (1981). Biochem. Soc. Symp. No. 46, 207–222.Google Scholar
  9. Finch, J.f., Perutz, M.F. Bertles, J.F. et al. (1973). Structure of sickled erythrocytes and sickle-cell hemoglobin fibers. Proc. Nat. Acad. Sci., USA, 718-722.Google Scholar
  10. Gorecki, M. Acquayes, C.T., Wilcheck, M., Votano, J.R. and Rich, A. (1980), Antisickling activity of amino acid benzyl esters. Proc. Natl. Acad. Sci., USA, 77, 181–185.CrossRefGoogle Scholar
  11. Gorecki, M., Votano, J.R. and Rich, A. (1980). Peptide inhibitors of sickle hemoglobin aggregation: Effect of hydrophobicity, Biochem. 19, 1564–1568.CrossRefGoogle Scholar
  12. Hagin, D.S., Weiner, J.H. and Skyes, B.D. (1970). Interaction of solvent accessibility on ferrotryrosyl residues of M13 cobalt protein in deoxycholate micelles and phospholipid vesicles. Biochem., 18, 2007–2012.Google Scholar
  13. Hendrick, W.R., Matthew, A., Simbrick, J.D. and Whaley, T.W. (1979). Intracellular viscosity of lymphocytes determined by an nitrogen-15 spin label probe. J. Mag. Reson., 36, 207–214.Google Scholar
  14. Johnson, M.E. and Zeidan, H. (1983). Probable binding region of small hydrophobic molecules on hemoglobin: spin label induced nuclear magnetic relaxation. Biochem. Biophy. Acta, 744, 193–199.CrossRefGoogle Scholar
  15. Kubota, S. and Yang, J.T. (1977). Oligopeptides as potential antiaggregation agents for deoxyhemoglobins Proc. Natl. Acad. Sci., USA, 74, 5431–5434.CrossRefGoogle Scholar
  16. Moffat, J.K., Simon, S.K. and Konigsberg, W.H. (1971). Structure and functional properties of chemically modified horse hemoglobin: Functional consequences of structural alterations and implications for molecular basis of cooperativity. J. Mol. Biol., 58, 89–101.CrossRefGoogle Scholar
  17. McCalley, R.C., Shimshick, E.J. and McConnell, H.M. (1972). Effect of slow rotational motion on paramagnetic resonance spectra. Chem. Phys. Lett., 143, 115–119.CrossRefGoogle Scholar
  18. Novak, R.F., Dershwitz, M. and Novak, F.C. (1978). The interaction of benzene with human hemoglolbin as studied by 2H Fourier Transform NMR spectroscopy. Biochem. Biophys. Res. Commun., 82, 634–640.CrossRefGoogle Scholar
  19. Novak, R.F., Dershwitz, M. and Novak, F.C. (1979). Characterization of the interaction of the aromatic hydrocarbons benzene and toluene with human hemoglobin. Mol. Pharmacol., 16, 1046–1058.Google Scholar
  20. Noguchi, C.T. and Schechter, A.N. (1977). Effects of amino acids on gelation kinetics and solubility of sickle hemoglobin. Biochem. Biophys. Res. Comm., 74, 637–642.CrossRefGoogle Scholar
  21. Noguchi, C.T. and Schechter, A.N. (1978). Inhibition of sickle hemoglobin gelation by amino acids and related compounds. Biochem., 17, 5455–5459.CrossRefGoogle Scholar
  22. Poillon, W.N. (1982). Noncovalent inhibitors of sickle hemoglobin gelation: Effects of aryl-substituted alanins. Biochem., 21, 1400–1406.CrossRefGoogle Scholar
  23. Poillon, W.N. (1980). Noncovalent inhibitors of sickle hemoglobin gelation: Effects of aliphatic alcohols, amides and ureas. Biochem., 19, 3194–3199.CrossRefGoogle Scholar
  24. Ross, P.D. and Subramanian, S. (1977). Inhibition of sickle cell hemoglobin gelation by some aromatic compounds. Biochem. Biophys. Res. Commun., 1217-1223.Google Scholar
  25. Seigneuret, M., Davonnst, J., Herre, P., and DeVaux, P. (1981). Fluorcarbohydrates: Synthesis, structure and characterization. Biochem., 63, 867–870.Google Scholar
  26. Skyes, B.D. and Hull, W.E. (1978). Experimental evidence for the role of cross relaxation in proton nuclear magnetic resonance spin lattice relaxation as measured in proteins. Methods Enzymol., 49, 270–295.CrossRefGoogle Scholar
  27. Skyes, B.D. and Weiner, J.H. (1980). Magnetic Resonance in Biology (Cohen, J.S., ed.) Vol. 1, pp. 171–196, John Wiley and Sons, NY.Google Scholar
  28. Sloan, D.L., Young, J.M. and Midlvan, A.S. (1975). Nuclear magneteic resonance studies of substrate interaction with cobalt substituted alcohol dehydrogenase from liver. Biochem., 14, 1998.CrossRefGoogle Scholar
  29. Stetter, E., Vieth, H.M. and Hausser, K.H. (1976). Studies of nitroxide radicals: Discrimination between rotational and translational correlation times in liquids. J. Mag. Res., 23, 493–504.Google Scholar
  30. Votano, J.R., Gorecki, M. and Rich, A. (1977). Sickle hemoglobin aggregation: A new class of inhibitors. Science 196, 1564–1568.CrossRefGoogle Scholar
  31. Wishner, B.C., Hauson, J., Ringle, J.W. and Love, W.E. (1976). In proceeding of the symposium on molecular and cellular aspects of sickle cell disease, pp 1-29, DHEW Publication No. 76-1007, Washington, DC.Google Scholar
  32. Wishner, B.C., Ward, k.B., Lattman, E.D. and Love, W.E. (1975). Crystal structure of sickle-cell deoxyhemoglobin at 5°A. J. Mol. Biol., 98, 179–194.CrossRefGoogle Scholar
  33. Zeidan, H., Watanabe, K., Piette, L.H., and Yasunobu, K.T. (1980). ESR spin label studies of bovine liver monoamine oxidase B., Frontiers in Protein Chemistry, (Mayamia, L.L., Liu, T-Y and Yasunobu, K.J., eds.), Elsevier, North Holland Press, pp 133-147.Google Scholar
  34. Zeidan, H. (1988). Interaction of spin-labeled tryptamine with monoamine oxidse: Probing the microenvironment of the active site by spin probe-spin label techniques. Biochem. Biophys. Acta, 955, 111–118.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Henry M. Zeidan
    • 1
  1. 1.Chemistry DepartmentAtlanta UniversityAtlantaUSA

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